吸入皮质激素治疗哮喘患者的骨密度、骨代谢变化及其危险因素

目的：探讨接受可吸入性皮质激素治疗-年以上的哮喘患者的骨质减少和骨质疏松的发病状况以及哮喘患者骨质减少和骨质疏松的危险因素。方法：自2007年8月到2011年7月,接受吸入性皮质激素治疗且治疗时间-年以上的哮喘患者为研究组,未接受吸入性皮质激素治疗的哮喘患者为对照组,哮喘患者年龄均在18岁以上。骨密度检测采用DEXA检测。骨质减少和骨质疏松采用WHOT—score评分。骨代谢指标包括血骨钙素以及碱性磷酸酶等,检测方法采用放免法进行。结果：研究对象共143名,其中研究组69例,对照组74例。研究组与对照组患者的血骨钙素水平分别为（3．8±2．4）、（2．7±1．4）μg／L,两组间无统计学差异（P=0．57）。两组患者的血碱性磷酸酶水平分别为（126±68）、（119±66）IU／L,两组间无统计学差异（P=0．37）。研究组和对照组患者的脊柱T—score评分均数分别为-0．72和-0．57（P=0．98）;股骨T—score评分均数分别为-0．60和-0．80（P=0．474）;髋骨T—score评分均数分别为0．19和0．06（P=0．275）。脊柱、股骨和髋骨T—score评分与年龄呈显著负相关,而与体重指数呈显著正相关。结论：哮喘患者骨质减少和骨质疏松危险因素是高龄和低体重指数,吸入皮质激素无累积效应。与对照组患者相比,吸入皮质激素治疗哮喘的患者没有其他的骨质减少和骨质疏松的危险因素。     

No association between inhaled corticosteroids and whole body DXA in postmenopausal women

PURPOSE: Postmenopausal women treated with corticosteroids are regarded as a high-risk group due to the effect of both natural bone loss and possible adverse effects of treatment with inhaled corticosteroids (IC). OBJECTIVE: To compare bone mineral density (BMD) in postmenopausal women exposed only to IC (IC group, n = 106) with that of BMD in women not exposed to corticosteroids (n = 124) and women exposed to oral and/or intra-articular injections in addition to inhaled corticosteroids (OC group, n = 31). The women were recruited from a population-based prospective cohort study. METHODS: Dual X-ray absorptiometry (DXA) technique was used to measure BMD in whole body, spine, pelvis and lower extremities. A health questionnaire and an interview about past and present medication use were used. RESULTS: The mean duration and dose of IC were 9.5 +/- 4.5 years and 615 microg daily. Whole body BMD did not significantly differ between the IC group (1.103 g/cm(2)) and the unexposed group (1.087 g/cm(2)). Within the IC group, BMD stratified for cumulative dose of IC, duration or current dose above or below 800 microg did not differ. Z-score BMD for tertiles did not differ when comparing the IC and OC groups. CONCLUSION: No difference in BMD was noted between postmenopausal women exposed to inhaled corticosteroids and unexposed controls nor was there any dose response relationship between inhaled corticosteroid therapy and BMD.     

Adverse skin reactions to inhaled corticosteroids

Inhaled corticosteroids are considered to be the therapy of choice in the treatment of asthma and allergic rhinitis. However, various cutaneous adverse reactions have been described and are probably present in approximately half of patients. Some of these reactions are related to the daily dosage of steroids or the duration of treatment, for example: thinning of the skin, easy bruising, acne or peri-oral dermatitis, mucocutaneous infection and, especially, candidiasis. Other cutaneous side effects are independent of the dose, such as allergic reactions and a few other rare side effects. Adverse effects could be prevented by monitoring the daily dosage and the family history of the patients, and by following advice provided on the use of inhaled corticosteroids. Specific treatments for infection, acne or allergy can cure these side effects. However, cutaneous side effects can become unpleasant for the patient and temporarily withdrawing therapy has proven to be extremely effective.     

儿童哮喘缓解期吸入性糖皮质激素用药依从性现况调查

目的：探讨儿童哮喘缓解期吸入性糖皮质激素（Inhaled Corticosteroids，ICS）用药依从性及影响因素。方法：对90名哮喘患儿家长进行问卷调查，分析患儿近3个月哮喘缓解期内ICS的使用情况、用药依从性、吸入装置掌握情况及相关影响因素。结果：患儿近3个月内使用最多的ICS为BUD （48.89%），其次是FP （35.56%）、BDP （6.67%）及其他（8.89%）。使用吸入装置最多的是雾化器（24.44%）和干粉吸入剂（都保）（24.44%），其次是压力定量气雾剂（加储物罐）（23.33%）、干粉吸入剂（准纳器）（14.44%）及压力定量气雾剂（无储物罐）（13.33%）。Morisky用药依从性量表调查结果显示，调查对象对于ICS的用药依从性平均得分为5.39，总体判定为依从性差（<6分）。影响依从性的主要影响因素是担心长期用药不良反应、病情好转后停药、各种原因引起的漏用、孩子治疗不配合、吸入装置复杂、用药后无效、用药方案复杂、家庭经济原因以及医师指导不到位等。结论：儿科临床医师和药师应进一步加强诊疗管理，强化吸入技术的使用培训，通过多种途径不断深化哮喘控制宣传、教育和培训工作，提高哮喘患儿长期用药依从性。     

呼出气一氧化氮指导支气管哮喘患者使用吸入性糖皮质激素治疗效果的研究

目的:对呼出气一氧化氮(fractional exhaled nitric oxide,FeNO)指导支气管哮喘患者使用吸入性糖皮质激素(in-haled corticosteroids,ICS)治疗效果的分析.方法:选取2019年1-12月在南京鼓楼医院呼吸与危重症医学科收治的支气管哮喘患者,共38例,根据初始FeN...     

吸入性皮质激素联合班布特罗治疗支气管哮喘的分析

目的观察吸入性皮质激素布地奈德联合班布特罗治疗支气管哮喘的疗效.方法将我院67例轻、中度哮喘患者随机分为两组,34例应用吸入性皮质激素布地奈德联合班布特罗与33例应用吸入性皮质激素布地奈德患者间治疗效果相比较得出结论.结果吸入性皮质激素布地奈德联合班布特罗能有效地控制哮喘急性发作及其相关症状和降低哮喘患者的住院率,减少布地奈德的吸入量.结论吸入性皮质激素布地奈德联合班布特罗治疗支气管哮喘优于单一吸入性激素布地奈德的疗效.     

The risk/benefit of inhaled corticosteroids in chronic obstructive pulmonary disease

Although inhaled corticosteroids have a well defined role in asthma therapy, their use remains controversial in nonasthmatic, smoking-related chronic obstructive pulmonary disease (COPD). Some studies have shown an effect of inhaled corticosteroids on airway inflammation in COPD, but the clinical relevance of these results is unknown. Data from five long-term, large studies, provide evidence that prolonged treatment with inhaled corticosteroids does not modify the rate of decline of forced expiratory volume in one second (FEV1) in patients with COPD and no reversibility to short-acting β₂-agonists. FEV1 was slightly improved over the first six months of treatment and lower reactivity in response to methacholine challenge has been observed. Improvement of respiratory symptoms and health status were also reported. A reduction of exacerbations rate was observed in two studies. No survival benefit was demonstrated. Two recent reports suggest that long term use of inhaled corticosteroids in COPD patients improves quality-adjusted life expectancy and is cost-effective. Combination therapy with inhaled corticos-teroids and long-acting β₂-agonists have proven benefit in four long term large studies compared to placebo for FEV1, exacerbation rate, symptoms and health status. However, only two studies found that combination therapy was more effective than long-acting β₂-agonists alone for symptoms and health status improvement. The long term safety of inhaled corticosteroids is not known in COPD patients but topical adverse effects, and systemic effects such as a decrease of bone density of lumbar spine and femur and cutaneous adverse effects, have been reported after three years of treatment. However, three recent observational studies found a slight increase in the risk of fractures (hip, upper extremities and vertebral) in association with high doses of inhaled corticotherapy.     

Adrenal suppression with high doses of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers

Study objective: This study was conducted to compare the adrenal suppression of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers, both given via their respective pressurised metered dose inhaler (pMDI) devices at high doses within the manufacturers recommended dose range. Design: We used a single (investigator) blind, randomised, crossover design comparing a total daily dose of 1.625 mg fluticasone propionate delivered via a pMDI, 1.60 mg daily of triamcinolone acetonide delivered via a pMDI with integrated spacer, or placebo pMDI; each drug was given in two divided doses at 0800 hours and 2200 hours over a 24-h period. Each drug treatment was separated by a 1-week washout. Patients: Twelve normal subjects mean age 27.5 years were studied. Measurements: Blood samples were taken for 0800 hours plasma cortisol, i.e. 10 h following the second dose. Ten hour urine collections (2200 hours until 0800 hours) were taken for urinary cortisol and creatinine excretion. Results: For the 0800 hours plasma cortisol (geometric mean, nmol · l⁻¹) compared with placebo (353) fluticasone propionate (138) produced significant (P<0.05) suppression (2.57-fold difference), whereas triamcinolone acetonide (263) did not (1.34-fold difference). Fluticasone propionate produced a 1.91-fold greater adrenal suppression than triamcinolone acetonide (95% CI 1.10 to 3.33). Individual subjects with abnormally low 0800 hours cortisol values <150 nmol · l⁻¹ (<5.4 μg/dl) were n=4 for fluticasone propionate and n=0 for triamcinolone acetonide. Overnight urinary cortisol/creatinine ratio (geometric mean, nmol/mmol) did not show any difference between fluticasone propionate (1.48) and triamcinolone acetonide (1.60), with both producing significant suppression versus placebo (4.01): triamcinolone acetonide 2.50-fold difference (95% CI 1.45–4.24); fluticasone propionate 2.71-fold difference (95% CI 1.57–4.69). Conclusion: Fluticasone propionate 1.625 mg/day (pMDI) produced an approximately two-fold greater adrenal suppression of 0800 hours plasma cortisol than triamcinolone acetonide 1.60 mg per day (Oral Inhaler) when given twice daily, and one third of subjects with fluticasone had abnormally low 0800 hours cortisol values <150 nmol · l⁻¹ (<5.4 μg · dl⁻¹). There were no differences between the drugs for urinary cortisol excretion. Further dose-ranging studies are required at steady-state in asthmatic subjects in order to see whether differences occur at lower doses on the steep part of the dose–response curve for both plasma and urinary cortisol suppression. Received: 28 January 1997 / Accepted in revised form: 11 April 1997     

鹿龟生骨丸对去卵巢大鼠骨代谢生化指标的影响

目的:研究鹿龟生骨丸对去卵巢大鼠骨代谢生化指标的影响,探讨鹿龟生骨丸治疗骨质疏松的作用机制。方法:采用去卵巢大鼠模型,分模型对照组、假手术组、鹿龟生骨丸组、雌激素对照组。去势1个月后鹿龟生骨丸组、雌激素对照组服药10周,放免法测定血清雌二醇(E2)、骨钙素(OC)、速率法测定血清碱性磷酸酯酶(ALP)及抗酒石酸酸性磷酸酶(TRACP),组间进行比较。结果:E2测定,用药后鹿龟生骨丸组、雌激素对照组E2水平均高于模型对照组,且都有极显著性(P<0.01)。雌激素对照组高于鹿龟生骨丸组,差异有显著性(P<0.05);OC测定,鹿龟生骨丸组、雌激素对照组均低于模型对照组,有显著性(P<0.05);ALP测定,鹿龟生骨丸组、雌激素对照组均低于模型对照组,有显著性(P<0.05);TRACP测定,用药后TRACP水平均下降,但雌激素对照组下降水平更接近假手术组,鹿龟生骨丸组与雌激素对照组相比无显著性(P>0.05)。结论:鹿龟生骨丸对绝经后骨质疏松有增加E2、促进骨形成、抑制骨吸收的作用。     

Anti-inflammatory effects of inhaled corticosteroids in chronic obstructive pulmonary disease: similarities and differences to asthma

Both chronic obstructive pulmonary disease (COPD) and asthma are characterised by the presence of airway inflammation. In the stable disease state, the predominant regulatory and effector cells, and the anatomic focus of the changes associated with airway inflammation, differ between COPD and asthma. However, during exacerbations, these patterns of inflammation become more similar. The benefit of anti-inflammatory therapy with inhaled corticosteroids (ICS) is well established in asthma, whereas the extent of the anti-inflammatory effects of ICS in COPD is debated. Understanding the distinctive and, in exacerbations, the changing patterns of inflammation in COPD and asthma allows a better appreciation of the potential for ICS to target the unique pathophysiology of COPD.     

Managing the safety of inhaled corticosteroids in COPD and the risk of pneumonia

Introduction: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease. To estimate the association between ICS and pneumonia among users of ICS relative to non-ICS users and to examine whether this risk is dose related, class related and what’s its association with the pneumonia-mortality or overall mortality.

Areas covered: Through a comprehensive literature search of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov from inception to February 2015, we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses to generate summary estimates comparing ICS with non-ICS treatment on the risk of pneumonia.

Expert opinion: ICS alone or in combination with long-acting β-agonists are associated with an increased risk of pneumonia but have no effect on pneumonia related mortality. It is important to identify those patients to benefit the most from ICS, as those with frequent exacerbations, a severe airway obstruction, a positive bronchodilator test or a sputum eosinophilia despite treatment.     

Safety of inhaled corticosteroids for treating chronic obstructive pulmonary disease

Introduction: The frequent use of inhaled corticosteroids (ICSs), especially at higher doses, has been accompanied by concern about both systemic and local side effects. Patients suffering from chronic obstructive pulmonary disease (COPD) are more at risk from side effects, likely because of the use of higher doses of ICS in COPD to overcome corticosteroid unresponsiveness.

Areas covered: There is considerable concern about increased incidence of pneumonia, osteoporosis and hyperglycemia in diabetic patients and cataracts. The local side effects of ICSs, such as hoarseness and pharyngeal discomfort, oral and oropharyngeal candidiasis, cough during inhalation, and a sensation of thirst, are not usually serious but are of clinical importance because they may lead to patients discontinuing therapy.

Expert opinion: The possibility that ICSs induce adverse side effects should not lead us to avoid their use in patients in whom clinical evidence suggests that they may be helpful. However, clinicians should balance the potential benefits of ICSs in COPD against their potential side effects and always consider using the lowest possible dose to achieve the best possible management.     

不同剂量地塞米松对大鼠松质骨代谢的影响

目的观察不同剂量地塞米松对大鼠松质骨骨代谢的影响。方法 31只SPF级3月龄SD♀大鼠,随机分为正常对照组、地塞米松(1、2.5及5 mg.kg-1)4个组,每周尾静脉注射给药2次,共8周。采用不脱钙骨切片和骨组织形态计量学方法观察和测量胫骨近端和第4腰椎的骨代谢参数。结果与正常组相比,地塞米松2.5及5 mg组胫骨上段骨小梁面积百分率增加;3个用药组的荧光周长百分率,骨形成率以及破骨细胞周长百分率都明显下降;而成骨细胞周长百分率只在5 mg组明显降低。腰椎骨小梁面积百分率增加差异没有显著性;但荧光周长百分率、骨形成率、破骨细胞和成骨细胞周长百分率降低差异都有显著性。结论地塞米松应用初期可能对骨代谢有促进作用而使胫骨上段骨量增加,但8周后对骨形成已经表现出明显抑制作用,并且有剂量依赖性,骨吸收也受到抑制,胫骨上段和腰椎的松质骨代谢都受到影响。     

骨化三醇对男性酒精性肝硬化患者骨密度和骨代谢的影响

目的：探讨补充骨化三醇对酒精性肝硬化患者骨密度和骨代谢指标的影响。方法：将维生素D缺乏的酒精性肝硬化患者随机分成观察组和对照组,两组常规治疗相同,观察组给予骨化三醇胶丸（0．25μg／d）治疗,比较两组治疗半年后骨密度及β胶原特殊序列（β-CTx）、25-羟维生素D（25-OHD）、血钙、血磷、甲状旁腺激素（PTH）等骨代谢指标的差别。结果：观察组治疗后血磷、PTH均较治疗前显著下降,25-OHD、血钙均较治疗前显著上升,差异均有统计学意义（P〈0．05）;对照组治疗后25-OHD较治疗前显著下降,差异有统计学意义（P〈0．05）;治疗后,观察组血钙和25-OHD显著高于对照组,血磷和PTH显著低于对照组,差异均有统计学意义（P〈0．05）;治疗后,观察组和对照组骨密度、T值、β-CTx和肝功能比较,差异无统计学意义（P〉0．05）。结论：补充骨化三醇半年可改善酒精性肝硬化患者维生素缺乏状态,但未发现能阻止骨破坏和提高骨密度。     

Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma

AIMS: To compare the pharmacokinetic profiles of beclometasone, budesonide, fluticasone and mometasone following inhalation in patients with asthma, and explore the relationship between lung function and plasma drug concentrations. METHODS: Thirty subjects with asthma and a forced expiratory volume in 1 s (FEV(1)) ranging from 36 to 138% predicted, inhaled 800 microg beclometasone, budesonide and mometasone and 1000 microg fluticasone in random order. Plasma drug concentrations were measured over 8 h and the relationship between the area under the plasma concentration-time curve (AUC(0-8)) and lung function was modelled using linear regression. Estimated AUC(0-8) values at 50 and 100% predicted FEV(1) were compared for each drug. RESULTS: Pharmacokinetic profiles differed markedly between the drugs. Correlation coefficients for the relation between FEV(1)% predicted and AUC(0-8) values for beclometasone, budesonide, fluticasone and mometasone were 0.37 (P = 0.05), 0.33 (P = 0.08), 0.25 (P = 0.2) and 0.52 (P = 0.004), respectively, and estimated AUC(0-8) values were 1.3 [95% confidence interval (CI) 1.0, 1.8], 1.3 (95% CI 1.0, 1.8), 1.4 (95% CI 0.9, 2.2) and 2.2 (95% CI 1.3, 3.5) times higher for the four drugs, respectively, at 100 compared with 50% predicted FEV(1.) CONCLUSION: The higher plasma concentrations of inhaled corticosteroids in patients with a higher FEV(1)% predicted suggests that, for any given dose, these patients will be at greater risk of developing adverse systemic effects with long-term use.     

长期使用质子泵抑制剂对老年患者骨代谢和骨密度的影响

目的 探讨长期使用质子泵抑制剂对老年患者骨代谢和骨密度的影响.方法 连续收集因反流性食管炎需要长期服用质子泵抑制剂的老年患者50例作为观察组,同期收集50例健康老年人作为对照组.比较两组的骨密度和骨代谢情况.结果 入组时,两组患者股骨颈骨密度差异无统计学意义(0.80 ±0.10 vs 0.79 ±0.09 g·cm-2,P=0.708).3个月和6个月时,观察组股骨颈骨密度均显著低于对照组[(0.73±0.10 vs 0.82±0.09 g·cm-2,P =0.000)和(0.68±0.11 vs 0.79 ±0.09 g·cm-2,P=0.000)].两组研究对象入组时降钙素、骨钙素、碱性磷酸酶和Ⅰ型胶原羧基末端肽均差异无统计学意义(P＞0.05).6个月时,观察组降钙素、骨钙素和碱性磷酸酶均显著低于对照组[(221.87 ±68.82 vs 251.53 ±58.72 ng·L-1,P=0.023)、(9.82 ±2.56 vs 11.66 ±2.88μg·L-1,P =0.001)、(10.47 ±2.18 vs 12.66 ±1.75μg·L-1,P =0.000)],Ⅰ型胶原羧基末端肽显著高于对照组(253.85 ±51.66 vs 225.39 ±52.88 ng·L-1,P=0.008).结论 长期使用质子泵抑制剂可导致骨破坏增加,进而导致骨质疏松.     

The impact of racial and ethnic disparities in inhaled corticosteroid adherence on healthcare expenditures in adults with asthma

Purpose: The purpose of this study is to determine racial and ethnic disparities with the adherence to inhaled corticosteroids (ICSs) in adults with persistent asthma, and their association with healthcare expenditures.

Methods: A retrospective, cross-sectional study using the Medical Expenditure Panel Survey (MEPS) 2013–2014 data included patients ≥18 years with persistent asthma. Median medication possession ratio (MPR) was used to dichotomize adherence levels. Multivariate regression analysis was conducted to ascertain the association between adherence and race/ethnicity. Total expenditures and association with adherence were analyzed using a generalized linear model with a log link function and gamma distribution. Unadjusted expenditures were compared after bootstrapping.

Results: The average MPR of ICSs for the sample of 277 patients was 0.34. The average MPR level was 0.33 among whites, 0.37 among African-Americans and 0.35 among other minorities. The average MPR was 0.30 among Hispanics, and 0.35 among non-Hispanics. African-Americans were less likely to be adherent than whites (OR 0.95). Hispanics were less likely to be adherent (OR 0.4; CI 0.206–0.777). Higher adherence was associated with significantly higher total health expenditure than lower adherence ($19,223 vs. $12,840 respectively, p?<?.0001). African-Americans had slightly higher total expenditure compared to whites; however, other minorities had significantly lower health expenditures compared to whites (p?=?.01). Non-Hispanics spent significantly less on healthcare compared to Hispanics (p?=?.04).

Conclusions: Valuable insight into the economic cost of the disparities as they relate to persistent asthma provides further evidence of possible ethnic inequities that warrant addressing.     

甲状腺机能亢进患者骨代谢指标的变化

目的　观察甲状腺机能亢进 (甲亢 )患者骨代谢指标的变化。方法　对 83例甲亢患者进行如下项目测定 :( 1)血钙 (Ca)、血磷 (P)、碱性磷酸酶 (AKP)、骨钙素 (BGP)、抗酒石酸酸性磷酸酶(TRAP) ;( 2 ) 2 4h尿Ca、P、羟脯氨酸 (HOP) ;( 3)尿Ⅰ型胶原氨基末端肽 (NTX) /Cr;( 4 )骨密度 (BMD)、胫骨骨超声 (SOS)。结果　甲亢患者的Ca、P、AKP、胫骨SOS与正常对照组没有显著差别 ;甲亢组的BGP、TRAP和 2 4h尿Ca、P、HOP、NTX/Cr、BMD与正常对照组没有显著差别 ;BGP与T3、FT3 有很好的相关性 (r=0 .38、0 .40 ,P <0 .0 1) ;NTX 与T3、T4 、FT3、FT4 有相关性 (r =0 .35、0 .4、0 .31、0 .45 ,P <0 .0 1)。结论　甲亢患者的骨吸收大于骨形成 ,BGP和NTX 不仅是观察甲亢患者骨代谢的重要指标 ,也是观察甲亢患者治疗效果的一个指标